Tokarski Krzysztof, Zahorodna Agnieszka, Bobula Bartosz, Hess Grzegorz
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland.
Exp Brain Res. 2002 Dec;147(4):505-10. doi: 10.1007/s00221-002-1259-6. Epub 2002 Oct 26.
The effects of serotonin (5-HT) as well as 5-HT(1A) and 5-HT(4) receptor agonists, (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) and zacopride, respectively, on population spikes evoked by electrical stimulation and on spontaneous epileptiform activity were investigated in CA1 area of hippocampal slices. Spontaneous epileptiform activity was recorded from slice in a nominally Mg(2+)-free medium. While 5-HT application resulted in a decrease of population spikes evoked in standard incubation conditions, in accordance with earlier studies, it exerted two opposite effects on epileptiform activity. The early inhibitory effect was mimicked by 8-OH-DPAT while the later, excitatory, by zacopride. The application of 8-OH-DPAT decreased, and that of zacopride increased, the amplitude of population spikes. A comparison of the dose-dependence of the excitatory and inhibitory effects of serotonergic agonists on the amplitude of the population spike and on the frequency of epileptiform discharges indicated that the latter is a more sensitive measure of the activation of 5-HT(1A) and 5-HT(4) receptors than the former. Thus, spontaneous epileptiform activity recorded in a nominally Mg(2+)-free slice medium represents a convenient model for investigation of hippocampal neuronal reactivity to the activation of various 5-HT receptor subtypes.
在海马切片的CA1区,研究了5-羟色胺(5-HT)以及5-HT(1A)和5-HT(4)受体激动剂,分别为(+/-)-2-二丙基氨基-8-羟基-1,2,3,4-四氢萘氢溴酸盐(8-OH-DPAT)和扎考必利,对电刺激诱发的群体峰电位以及自发癫痫样活动的影响。在名义上无镁(Mg(2+))的培养基中记录切片的自发癫痫样活动。与早期研究一致,虽然应用5-HT会导致在标准孵育条件下诱发的群体峰电位降低,但它对癫痫样活动产生了两种相反的作用。早期的抑制作用可被8-OH-DPAT模拟,而后期的兴奋作用可被扎考必利模拟。应用8-OH-DPAT会降低,而应用扎考必利会增加群体峰电位的幅度。对5-羟色胺能激动剂对群体峰电位幅度和癫痫样放电频率的兴奋和抑制作用的剂量依赖性进行比较表明,后者是比前者更敏感的5-HT(1A)和5-HT(4)受体激活指标。因此,在名义上无镁的切片培养基中记录的自发癫痫样活动代表了一种方便的模型,用于研究海马神经元对各种5-HT受体亚型激活的反应性。